Receptive sites on postsynaptic membranes are considered the key to specificity in chemical neurotransmission. We propose to continue our study of high affinity, limited capacity receptors for gamma-aminobutyric acid (GABA). Using techniques previously established in our laboratory, we will isolate and characterize 3 receptive sites for GABA which subserve distinct functions in the mammalian central nervous system. These are the transport receptive sites for neurons and glia and the postsynaptic receptor. Microsomal fractions of cerebral and cerebellar cortical tissue serve as the source of glial transport receptive sites while synaptic plasma membranes and synaptic junctional complexes are the source of neuronal transport and postsynaptic receptive sites respectively. Receptive sites solubilized from these membrane franctions will be employed as starting meterials for purification via gel filtration, ion exchange, hydrophobic and/or affinity chromatography. Membrane bound and soluble receptive sites will be characterized chemically, physically and pharmacologically. Long range goals include purification to homogeneity, preparation of antibodies, and immunohistochemical localization of all 3 receptive species for GABA. In addition, mechanistic studies of the receptive sites employing artificial membranes are anticipated.